The objectives of the proposed research are to use the guinea pig ileum as a model for studying the acute effects of opiates and tolerance. Development of opiate receptors and physiological responses will be determined in relation to the ontogeny of adrenergic, cholinergic, serotonergic, and non-adrenergic inhibitory neurons. The effects of chronic exposure to morphine during development will be examined. Organotypic tissue cultures will be used to help differentiate the mechanisms underlying acute effects of opiates from those underlying tolerance. Information derived from experiments on gut will also be tested in the CNS.